Method of stabilizing organic compounds against oxidation with dopa or dopa derivatives

ABSTRACT

Small amounts of DOPA and DOPA derivatives of the formula   AND THEIR ACID ADDITION SALTS RETARD OXIDATION OF FATS, OIL, PLASTICS, RUBBERS, AND OTHER ORGANIC COMPOUNDS BY ATMOSPHERIC OXYGEN, WHEN R is hydrogen, or alkyl having up to 24 carbon atoms, and R&#39;&#39; is hydrogen or alkanoyl having two to 24 carbon atoms.

United States Patent 1 1 Ninagawa et al.

[451 May 13,1975

[ METHOD OF STABILIZING ORGANIC COMPOUNDS AGAINST OXIDATION WITH DOPA OR DOPA DERIVATIVES [75] Inventors: Sadayoshi Ninagawa, Yokohama;

Shito Takeshita, Kawasaki, both of Japan [73] Assignee: Ajinomoto Co., Inc., Tokyo, Japan [22] Filed: Aug. 17, 1973 [21] Appl. No.: 389,205

[30] Foreign Application Priority Data Sept. 1, 1972 Japan 47-87790 [52] US. Cl. 426/544; 426/610; 252/403 [51] Int. Cl A23d 5/04 [58] Field of Search 426/181, 182, 228, 328;

[56] References Cited OTHER PUBLICATIONS Chemical Abstracts, V01. 55, 1961, 20457h, Kaufmann et a1.

Chemical Abstracts, Vol. 75, 1971, 13755411, Bell at al.

Primary ExaminerNorman Yudkoff Assistant ExaminerCurtis P. Ribando Attorney, Agent, or Firm-Hans Berman and their acid addition salts retard oxidation of fats, oil, plastics, rubbers, and other organic compounds by atmospheric oxygen, when R is hydrogen, or alkyl having up to 24 carbon atoms, and R is hydrogen or alkanoyl having two to 24 carbon atoms.

5 Claims, No Drawings 1 METHOD OF STABILIZING ORGANIC COMPOUNDS AGAINST OXIDATION WITH DOPA OR DOPA DERIVATIVES This invention relates to the protection of organic compounds against oxidation by atmospheric oxygen, and particularly to a method of stabilizing such organic compounds against oxidation.

Oils of animal, vegetal, or mineral origin, fats, rubbers, paraffin wax, synthetic resins, and like organic materials are sensitive to atmospheric oxygen, and deteriorate in storage due to contact with air. It is known to admix small amounts of butylated hydroxyanisole (Bl-IA), butylated hydroxytoluene (BHT-), ascorbic acid and its salts to oxygen-sensitive organic materials, but there is a need for other antioxidants which are more effective and/or less toxic to humans.

It has now been found that DOPA and its derivatives of the formula HO CH ca-coon are effective antioxidants in amounts so small as to be without significant toxicity to humans. In this formula, R is hydrogen, or alkyl having up to 24 carbon atoms, and R is hydrogen or alkanoyl having 2 to 24 carbon atoms. Particularly effective are the DOPA derivatives where R is hydrogen and R is alkyl having 4 to 24 carbon atoms.

The compounds of the invention are water-soluble when R is hydrogen and are soluble in fats, oils, and like organic compounds when R is alkyl. They also form acid addition salts with hydrochloric, sulfuric, tartaric, succinic, oxalic, ascorbic, p-toluene-sulfonic, pyrrolidonecarboxylic, acetic acid, and a wide variety of other acids having a first dissociation constant lower than those of the acids specifically enumerated, and the salts are generally as effective as equimolecular amounts of the free cationic moiety.

The esters of the invention are readily prepared from 3,4-dihydroxyphenylalanine (DOPA) and N-alkanoyl DOPA or salts thereof with suitable alkylating agents, such as the dialkyl sulfates, alkyl halides, and alkylene oxides, as is conventional in itself, and the esters, particularly those of alcohols having at least four carbon atoms, and other oil soluble compounds of the invention effectively inhibit oxidation of fatty and oily triglycerides, such as vegetable oils, animal fats, fish oils, also liquid and solid hydrocarbons including paraffin wax, petroleum fractions including lubricants and' tives of this invention, and similar beneficial effects have been observed in various oxygensensitive insecticide compositions and medicines, the water soluble compounds of the invention being employed in aque- 5 ous solutions or dispersions of oxygen-sensitive organic compounds.

The N-alkanoyl derivatives are prepared in a conventional manner by reaction of acetyl chloride, lauroyl chloride, stearoyl chloride and the like with DOPA or its esters.

The anti-oxidant application of DOPA and the DOPA derivatives has been tested most extensively so far in the protection of edible fats and oils, the fatty acids derived from these fats and oils, and the soaps which are alkali metal salts of the fatty acids. The fats and oils which can be stabilized with very small amounts of DOPA and the DOPA derivatives include butter, margerine, soy bean oil, cotton seed oil, sesame oil, rape seed oil, olive oil, corn oil, peanut oil, fish oils generally, the fatty acids derived from such fats and oils including oleic acid, linoleic acid, linolenic acid, arachidonic acid, and the soaps which are alkali metal salts of the acids.

The amount of DOPA or DOPA derivative that is intimately mixed with the organic material to be stabilized varies with the degree of stabilization required, with the presence or absence of other stabilizing materials, the nature and purity of the material to be protected against oxidation, and other factors. Generally, measurable protection can be had with as little as 0.00l% of DOPA or its derivatives, as defined above, and no further benefits can be achieved by increasing the admixture to more than 1%, all percentage values herein being by weight unless specifically stated other- 5 wise.

The optically active and inactive forms of DOPA and of its derivatives, as defined above, are equally effective antioxidants.

The following Examples further illustrate the preparation and use of anti-oxidants according to the invention.

EXAMPLE l 7.88 g L-DOPA, 3.52 g namyl alcohol, 7.98 g p-toluenesulfonic acid, and 70 ml toluene were refluxed in a l00 ml 3-neck flask equipped with a stirrer, Dean- Stark water trap, reflux condenser, and thermometer for 3 hours. The toluene thereafter was removed in a vacuum, and a residue of l6.8 g of white crystals was obtained. They had a melting point of 102 to 104C, and were identified as the p-toluenesulfonic acid addition salt of DOPA n-amyl ester by elementary analysis.

Calculated for C H NO S Found 57.39% C, 6.65% H, 3. l9% N, 7.29% S 57.] l 6.78 3.05 7.02

The crystals were dissolved in ethanol, and the solution was neutralized with an ethanol solution of potas- 60 sium hydroxide at 0C. The neutral solution was diluted with water and extracted with toluene. The extract was washed with water and evaporated in a vacuum to yield 8.1 g LDOPA n-amyl ester melting at 85 88C and identified by elementary analysis.

Calculated for C H NO Found 62.90% C, 7.92% H, 5.24% N 63.47 8.30 4.93

EXAMPLE 2 l 1.82 g L-DOPA, l5.60 g n-octyl alcohol. and 70 ml benzene were refluxed as in Example l while hydrogen chloride gas was fed to the solution. After five hours of low instead of soy bean oil, and the results are tabulated in an analogous manner in Table I].

5 refluxing, the benzene was removed, the reaction mix- TABLE II ture was neutralized with aqueous sodium carbonate solution and extracted with chloroform. The extract Anti- Peroxide Value was washed with water, and crystalline L-DOPA n- Oman 5 20 octyl ester was recovered by vacuum evaporation of 10 None 42 125 1803 the chloroform. The yield, after recrystallization from I 3.8 ms 43 petroleum ether, was .8 g. The white crystals melted 3 3- at 94 to 98C. and were identified by elementary anal- VI ysis.

Calculated for CHHNNO, 66.04% C. 8.80% H, 4.53% N Found 66.21 8.78 4.42

Other novel esters and acid addition salts of esters EXAMPLE 5 prepared by conventional methods such as those illus- R iv b h f a second r f soy b i] trated in Examples 1 and 2 included: were mixed with amounts of DOPA lauryl ester (ll) DOPA lauryl ester m.p. l0S to l08"C p-Toluenesulfonic acid salt of DOPA lauryl ester m.p. 85 to 88C DOPA cctyl ester 94 to 96C DOPA stearyl ester 105 to 107C p-Toluenesulfonic acid salt of DOPA stcaryl ester 60 to 64C EXAMPLE 3 varying from 0.0005 to 0.02%, and with 0.02% BHT Respective batches of the same lot of soy bean oil The mlxturfas l a batch of unm lxed wem f were mixed thoroughly with 002% the antioxidants ected to the oxidation test described In Example 3 w|th identified by Roman numerals as follows: the results shew m Table l BHT I] L-DOPA lauryl ester TABLE "I ll] L-DOPA pentyl ester [V N-lauroyl-L-DOPA v NSearOyLbDOPA Anti- Peroxide Value VI N-acetyl-L-DOPA ethyl ester oxidant 5 10 20 hm N 5.9 39.7 6799 Each mixture was held at 97.8C while a uniform, 33; 52 213 1516 constant stream of arr was bubbled through the hot 011. 0.0005% II 4.5 30.6 703.6 The peroxide value of each batch was determined after 3&3: :2 2: 322 5, l0 and 20 hours in milliequivalent of peroxide O:01% formed per kilogram of oil. For comparsion purposes, 002% II 4.0 3.7 8.5 a control batch of oil free from antioxidant was subjected to the same treatment. The results are listed in Table 1 below. EXAMPLE 6 TABLE 1 Respective batches of a third lot of soy bean oil were mixed wth 0.02% antioxidant partly identified in Exam- Anm peroxide value pie 3 and the following salts of esters identified by sym- Oxidant 5 hrs. l0 hrs. 20 hrs. bols:

None 3.8 38.2 766.0 lla L-DOPA lauryl ester pyrrolidonecarboxylic acid salt In 6 [lb L-DOPA lauryl ester ascorbic acid salt llc L-DOPA lauryl ester tartaric acid salt IV 4.8 7.3 49.8

llla L-DOPA pentyl ester hydrochloric acid salt V lllb L DOPA I 1 If 'd V] pfinly BStf l0 uenesu 0111C 3C! sat The results of oxidation tests erformed in the manner p EXAMPLE 4 of Example 3 are listed below in Table IV together with The procedure of Example 3 was repeated with talthose obtained with a control free from antioxidant.

What is claimed is:

l. A method of protecting an organic material against oxidation which comprises mixing said material with an anti-oxidant which is a compound of the formula uo cn ca 2 l 2 H" V or an acid addition salt of said compound,

- COOR a. in said formula R being alkyl having 4 to 24 carbon atoms,

b. said material being an oil, fat, or wax of animal, vegetal, or mineral origin and sensitive to oxidation by atmospheric oxygen, and

c. the amount of said antioxidant being sufficient to retard said oxidation.

2. A method as set forth in claim 1, wherein said material is an edible oil or fat, and the amount of said antioxidant is between 0.001% and l.0% of the weight of said material.

3. A method as set forth in claim 1, wherein said antioxidant is an addition salt of said compound with hydrochloric, sulfuric, tartaric, succinic, oxalic, ascorbic, p-toluenesulfonic, pyrrolidonecarboxylic, or acetic acid.

4. A method as set forth in claim 1 which further comprises exposing the resulting mixture of said material and of said compound to atmospheric oxygen until said material is partly oxidized by said oxygen 5. A method as set forth in claim 1, wherein said sufficient amount of said antioxidant is not greater than one percent of the weight of said material. 

1. A METHOD OF PROTECTING AN ORGANIC MATERIAL AGAINST OXIDATION WHICH COMPRISES MIXING SAID MATERIAL WITH AN ANTIOXIDANT WHICH IS A COMPOUND OF THE FORMULA
 2. A method as set forth in claim 1, wherein said material is an edible oil or fat, and the amount of said antioxidant is between 0.001% and 1.0% of the weight of said material.
 3. A method as set forth in claim 1, wherein said antioxidant is an addition salt of said compound with hydrochloric, sulfuric, tartaric, succinic, oxalic, ascorbic, p-toluenesulfonic, pyrrolidonecarboxylic, or acetic acid.
 4. A method as set forth in claim 1 which further comprises exposing the resulting mixture of said material and of said compound to atmospheric oxygen until said material is partly oxidized by said oxygen.
 5. A method as set forth in claim 1, wherein said sufficient amount of said antioxidant is not greater than one percent of the weight of said material. 